What are the potential side effects of stimulant medications, such as Ritalin (methylphenidate) or Adderall (amphetamines), in children with Attention Deficit Hyperactivity Disorder (ADHD)?

Side Effects of Stimulant Medications in Children with ADHD

Stimulant medications for ADHD in children are associated with predominantly mild and transient side effects, with the most common being decreased appetite, sleep disturbances (insomnia), abdominal pain, and headaches, while serious adverse events are rare. 1

Common Non-Serious Side Effects

The most frequently reported adverse effects occur more often with stimulants than placebo and include 1:

• Decreased appetite - highly frequent and dose-related for both methylphenidate and amphetamines 1
• Sleep onset delay/insomnia - common across all stimulant formulations 1
• Abdominal pain and stomachache 1
• Headaches 1
• Weight loss 1
• Jitteriness 1

These side effects are generally mild, transient, and responsive to dose or timing adjustments. 1 Careful lowering of the dose or changing the timing of administration may alleviate these effects. 1

Growth and Development Effects

Stimulants cause statistically significant reductions in both height and weight gain, with effects appearing dose-related and similar for both methylphenidate and amphetamine. 1

• The MTA study revealed more persistent effects on growth velocity than previous studies, particularly with higher and more consistently administered doses 1
• Diminished growth is typically in the range of 1-2 cm 1
• Effects diminished by the third year of treatment, though no compensatory rebound was found 1
• Whether effects on height are reversible remains unclear 1
• Reduced appetite plays a major role, but other mechanisms such as hormonal dysregulation may contribute and require further investigation 1

Growth should be monitored during treatment. 2

Cardiovascular Concerns

Sudden cardiac death in children on stimulant medication is extremely rare, and evidence is conflicting as to whether stimulants increase this risk. 1

• Expand history to include specific cardiac symptoms, Wolf-Parkinson-White syndrome, sudden death in the family, hypertrophic cardiomyopathy, and long QT syndrome 1
• Methylphenidate is safe in healthy children and has shown no cardiac side effects in these patients 3
• High-dose overdose can cause tachyarrhythmias, hypertension or hypotension, vasospasm, myocardial infarction, or aortic dissection that may precipitate sudden cardiac death 4

Psychiatric and Neurological Side Effects

Uncommon but significant psychiatric adverse effects include hallucinations and other psychotic symptoms. 1

• Stimulants may exacerbate symptoms of behavior disturbance and thought disorder in psychotic pediatric patients 2
• Amphetamines have been reported to exacerbate motor and phonic tics and Tourette's syndrome 2
• Clinical evaluation for tics and Tourette's syndrome in pediatric patients and their families should precede use of stimulant medications 2
• Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have been observed with CNS stimulant abuse and/or misuse 4
• Atomoxetine (non-stimulant) carries risk of increased suicidal thoughts (less common) 1

Age-Specific Considerations

Preschool-Aged Children (4-5 years)

Preschool-aged children may experience increased mood lability and dysphoria with stimulants. 1

• Evidence suggests slower metabolism of methylphenidate in children 4-5 years of age, requiring lower starting doses with smaller incremental increases 1
• Concerns exist about longer-term effects on growth and brain development in this population 1
• Lack of information about effects on brain development warrants consultation with a mental health specialist experienced with preschool-aged children 1

Adolescents

Diversion and misuse of ADHD medication is a special concern among adolescents. 1

• Monitor for signs of misuse or diversion of medication, including by parents, classmates, or other acquaintances 1
• Consider prescribing nonstimulant medications that minimize abuse potential (atomoxetine, extended-release guanfacine, extended-release clonidine) when diversion risk is high 1

Serious Adverse Events and Overdose

Serious side effects are rare and short-lived if medication is reduced in dose or discontinued. 1

• Severe movement disorders, obsessive-compulsive ruminations, or psychotic symptoms are very rare and disappear when medication is stopped 1
• Life-threatening hyperthermia (temperatures >104°F) and rhabdomyolysis may develop with overdose 4
• Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur with overdose 4
• Takotsubo cardiomyopathy may develop 4

Substance Use and Dependence

Methylphenidate and amphetamines have high potential for abuse and misuse, which can lead to substance use disorder. 4

• Physical dependence may develop, manifested by withdrawal symptoms after abrupt discontinuation (dysphoric mood, depression, fatigue, vivid unpleasant dreams, insomnia or hypersomnia, increased appetite, psychomotor changes) 4
• Tolerance may develop, requiring higher doses to achieve the same effect 4
• Evidence suggests psychostimulants reduce the risk of substance abuse, criminality, and suicidal events when used therapeutically 1

Comparative Side Effect Profiles

Both methylphenidate and amphetamine formulations have similar adverse effect profiles, with effects being predominantly mild and/or temporary. 1

• Approximately 43% of responders show preferential response to only one stimulant formulation, suggesting individual variation in tolerability 5
• Decreased appetite and insomnia are more common at higher dose levels for both stimulants 5
• Non-stimulant atomoxetine causes initial somnolence and gastrointestinal symptoms, particularly with rapid dose escalation, plus decreased appetite and rare hepatitis 1
• Alpha2-agonists (extended-release guanfacine and clonidine) cause somnolence and dry mouth 1

Monitoring Recommendations

Periodic assessment is essential, potentially including medication-free intervals, to determine continued need for treatment. 1

• Monitor for common side effects at each visit 1
• Track growth parameters (height and weight) regularly 2
• Assess for emergence of tics or psychiatric symptoms 2
• More frequent appointments should be scheduled if side effects occur, significant comorbid impairment exists, or adherence problems arise 1